There is interest in methods for the synthesis of large numbers of diverse compounds which can be screened for various possible physiological or other activities. Techniques have been developed in which one adds individual units sequentially as part of the chemical synthesis to produce all or a substantial number of the possible compounds which can result from all the different choices possible at each sequential stage of the synthesis. See e.g., Still et al., PCT Appli. WO94/08051. For techniques such as these to be successful, numerous solid state chemical reactions must be developed.
Ellman et al., ("Progress Toward the Synthesis of a Library of 1,4-Benzodiazepin-2,5-diones" ACS National Meeting, Anaheim, Calif. Apr. 2-6, 1995, Abstr. ORGN264) have reported a solid-phase synthesis of 1,4 benzodiazepin-2,5-diones. The Ellman et al. method limits the diversity of the benzodiazepin-2,5-dione scaffold because attachment of the scaffold to the solid support during synthesis is through the benzene ring, a residuum remaining on said ring after detachment of the benzodiazepin-2,5-dione from the solid support. Solution-phase synthesis of 1,4 benzodiazepin-5-ones via intramolecular aza-Wittig reaction has been disclosed by Egushi et al. (SYNLETT, 295-6, April 1992).
It is also desirable for compounds produced by combinatorial synthesis to be amenable to methods by which one can determine the structure of the compounds so made. Brenner and Lerner (PNAS USA 81: 5381-83 (1992)) and WO 93/20242, for example, describe a synthesis wherein oligonucleotides are produced in parallel with and are chemically linked as genetic tags to oligopeptides as the compounds of interest. WO 93/06121 teaches methods for particles-based synthesis of random oligomers wherein identification tags on the particles are used to facilitate identification of the oligomer sequence synthesized. A detachable tagging system is described in Ohlmeyer et al., Proc. Natl. Acad. Sci. USA, 90, 10922-10926, December 1993.